According to the National Cancer Institute, the foundations of cancer treatment have typically been surgery, chemotherapy, and radiation therapy, Now however, immunotherapy has become what many in the cancer community now call the “fifth pillar” of cancer treatment.
In this podcast, Gregory B. Lesinski, PhD, MPH, and Bassel El-Rayes, MD , discuss the exciting world of immunotherapy, the breakthroughs that are being discovered at Winship Cancer Institute of Emory University, and when to refer to a specialist.
Selected Podcast
Part One: Understanding Immunotherapy: A Breakthrough in Cancer Treatment
Featuring:
Learn more about Gregory B. Lesinski, PhD, MPH
Bassel El-Rayes, MD is the chief clinical research scientist responsible for coordinating and providing high-level direction to the clinical cancer research programs and clinical cancer trials across the Emory campuses. El-Rayes is Professor and Vice Chair for Clinical Research of the Department of Hematology and Medical Oncology at Emory University School of Medicine and has served as Director of the Winship Gastrointestinal Oncology Program since joining Winship Cancer Institute in 2009. Board certified in hematology and medical oncology, he treats patients with gastrointestinal malignancies.
Learn more about Bassel El-Rayes, MD
Gregory B. Lesinski, PhD, MPH & Bassel El-Rayes, MD
Gregory B. Lesinski, PhD, MPH, is Associate Professor in the Department of Hematology and Medical Oncology at Emory University School of Medicine in Atlanta, Georgia. Since 2008, the Lesinski research team has focused on the interactions between the immune system and cancer. This knowledge is being leveraged to develop novel therapeutic approaches for patients with cancer, and improve upon existing therapies.Learn more about Gregory B. Lesinski, PhD, MPH
Bassel El-Rayes, MD is the chief clinical research scientist responsible for coordinating and providing high-level direction to the clinical cancer research programs and clinical cancer trials across the Emory campuses. El-Rayes is Professor and Vice Chair for Clinical Research of the Department of Hematology and Medical Oncology at Emory University School of Medicine and has served as Director of the Winship Gastrointestinal Oncology Program since joining Winship Cancer Institute in 2009. Board certified in hematology and medical oncology, he treats patients with gastrointestinal malignancies.
Learn more about Bassel El-Rayes, MD
Transcription:
Melanie Cole (Host): Welcome to Emory Healthcare Rounds. I'm Melanie Cole. Today, you are listening to part one of our conversation on the latest advances in immunotherapy, and my guests are Dr. Bassel El-Rayes. He’s a gastrointestinal oncologist in the department of Hematology and Medical Oncology at Emory University School of Medicine and Vice Chair for Clinical Research at Winship Cancer Institute of Emory University. And Dr. Gregory Lesinski. He’s an Associate Professor in the Department of Hematology and Medical Oncology at Emory University School of Medicine and the Co-Director of Translational GI Malignancy Program at Winship Cancer Institute where his primary research interests include immunotherapeutics. Welcome to the show gentlemen. So, El-Rayes, I’d like to start with you. What is the evolution of immunotherapy and how do you see it breaking on to the cancer scene?
Dr. Bassel El-Rayes, MD (Guest): Thank you for that interesting question. For a long time, we have known that the immune therapy is a venue to treat cancer, but we have not been able to take that information from the lab into the clinic successfully. Recently, in the past few years, with the development of a new class of antibodies, called check point inhibitors, we started seeing the fruit of the work that was done for many years in the lab. We started to see drugs come into the clinic that can stimulate the immune system to fight the cancer. Of course, this is a new approach for cancer therapeutics and it appears to be a very promising approach. Since the introduction of that first class of drugs there are a number of additional classes of drugs that are now being looked at and researched in different cancers. These drugs target different aspects of the immune system, trying to stimulate the body to fight the cancer and most people in the field feel that immune therapy is the path forward for cancer therapeutics in the near future.
Melanie: And Dr. Lesinski, once of the most fascinating aspects for other physicians seems to be that immunotherapy can turn off cancer cells’ abilities to develop into tumors and how are you exploring ways to boost immune cells’ capacity to fight back. It is teaching these little soldiers as it were. Please outline for us the basic principles of cancer immunotherapy.
Dr. Gregory Lesinski, PhD, MPH (Guest): So, yeah, the basic principles of cancer immunotherapy are different than a conventional therapeutic approach for advanced malignancy in that the target of the drugs and the approaches used are really the body’s own white blood cells and immune system as opposed to interacting with the developing tumors themselves. So, this is really a paradigm shifting way to establish a living drug within the body either derived from a patient’s own immune system or even more complex cellular approaches where patient’s white blood cells are taken out of the body, educated in a certain way and put back into the body with a cancer fighting capacity in the setting of adoptive cell therapy or CAR-T cells. As Dr. El-Rayes had mentioned earlier, the immune system is activated by cancers but in many cases it is shut off, so what people are looking at including investigators at Winship Cancer Institute, are ways to overcome those shut off switches by giving drugs or in fact learning more about how cancers will paralyze the immune system through soluble factors that they may produce as well as really transformations of the way the immune system looks and functions in those patients.
So, the path forward in this whole field, is really trying to advance on this exciting data with single agent immunotherapies such as these check point inhibitor antibodies where in many patients with advanced disease, normally they would receive conventional therapy; here in many situations, they will receive these immunotherapies and have regressions of long-term metastatic disease. So, we are now looking into combination therapy approaches by combining multiple immunotherapies at the same time or with other small molecules that may target the cancer cells directly or in essence with more conventional therapies like radiotherapy or chemotherapy. All this work is ongoing, and we predict that many new exciting findings will emerge within the next few years as some of the early phase clinical trials and research completes.
Melanie: Dr. El-Rayes, as we hear about all of these different types of immunotherapy from adoptive cell transfer and even possibly vaccines, treatment vaccines; who do you envision this to be most beneficial for? Who are going to be appropriate candidates for these types of therapies?
Dr. El-Rayes: I think on the long-term hopefully it will be applied in the majority of cancers and in patients mainly who have – now it is being studied in patients who have advanced stage disease but there is interest in studying even an earlier staged disease to try and prevent cancer recurrences. So, I think this approach of using either medications to stimulate the immune system, vaccines, adoptive T-cell technologies between those different methods to stimulate the immune system will be used in treatments of the majority of cancers in the future and hopefully they will be used in early stage as well as late-stage disease.
Melanie: Dr. Lesinski, back to you. You mentioned Car-T cell therapy before and some of these types of immunotherapies can cause some side effects, some worrisome side effects. What are some of the risks and benefits that you would lay out to patients based on the fact that you are using these living – this kind of living organism to help fight their immune system?
Dr. Lesinski: Yeah, that’s a great question and a great point. Anytime you really unleash the body’s ability to react against a tissue, like a tumor that is considered self in many ways, you inherently open up the door for a variety of risks and as people have observed clinically, one of the major side effects from immune therapy are various toxicities that are autoimmune in nature and these are to be taken very seriously. Many of them can obviously be managed with steroids to quell that reaction, however, in many cases, they can in fact become quite serious.
So, these are definitely risks that need to be taken into account when a patient considers an immunotherapy type treatment approach or experimental trial, and these are also things that in the laboratory and the clinic, people are actively studying to better understand the mechanisms of those toxicities and whether the benefit is linked with appearance of them. So, just as an example, in many patients who have melanoma, skin cancer, who receive immunotherapy, they will often get a syndrome called vitiligo where the pigment is reduced in the body as a direct result of attacking melanin producing cells by the immune system. This in itself is often closely linked with efficacy of these immunotherapies, so in that essence many of these off-target effects or on target effects that are autoimmune in nature can actually be signs that the drugs are working.
So, this is a very curious area and on the flip side, there have been some recent reports I believe in the New England Journal from a Jedd Wolchok and his group at Memorial who have shown that the zealous response of the immune system against tumors such as one in maybe the bowel, metastatic melanoma when the T-cells would recognize it you can actually lead to a perforation resulting in unanticipated toxicity. So, this is a case where unlike other therapies, the side effects can result from a dramatic efficacy of treatment as well as sort of the basic autoimmune reactions that you might expect. The risks of – so that’s speaking to the risks of immunotherapy, but certainly the benefits of immune therapy are huge in that many patients again who would have progressed on multiple other treatment options can really have long durable regressions of disease and in many cases complete responses that don’t recur. A lot of this work has been seen very dramatically in lung cancer referred to as the Lazarus effect as well as in melanoma, renal cell carcinoma, and some of the colon cancers and other tumors that have micro satellite instability as a genetic marker. So, that’s sort of my understanding of the risks and benefits within the immunotherapy space and a few examples of how those might be used clinically as well as in our planning when patients are administered these agents.
Melanie: Dr. El-Rayes, Dr. Lesinski just said it might be used in planning. So, what’s going on right now as far as FDA approved treatments and he mentioned melanoma and lung cancer, we have heard of CAR-T cell for even children’s treatments of leukemia and such so where are we in FDA approval for the different types of cancer and immunotherapies?
Dr. El-Rayes: So, in the past few years, we have had a number of FDA approvals for the class of drugs called check point inhibitors. Like we said, those are antibodies that stimulate the specific type of lymphocytes to recognize the cancer. The drugs are now approved in melanoma, and lung cancer and cancers of the head and neck and then in stomach cancer, liver cancer. They are also approved recently in a special kind of colon cancer called MSI High colon cancer or otherwise known as Lynch syndrome. These are some examples of cancers that have recently – where we have recently demonstrated that check point inhibitors have clinical activity and we were able to meet bars set by the FDA to get approval for those medications. In addition, those medications are approved in some of the blood cancers like Hodgkin’s disease. Now the CAR-T cells have been approved in lymphoma and in a kind of leukemia called ALL which as you mentioned earlier affects children and then there are a number of other compounds that are getting close to being approved but not yet approved that are in late stage clinical development that target the immune system as well.
Melanie: Absolutely fascinating gentlemen. This concludes part one of our special two part series on immunotherapy. We invite you to listen to part two in order to hear the rest of this fascinating interview. Winship Cancer Institute of Emory University is an NCI comprehensive cancer center. Should you have questions or wish to discuss the care of your patients please use our referral form or call us at 888-WINSHIP, that's 888-946-7447. You're listening to Emory Healthcare Rounds. For more information on Winship Cancer Institute of Emory University, please visit www.emoryhealthcare.org/referwinship that's www.emoryhealthcare.org/referwinship . I'm Melanie Cole. Thanks so much for tuning in.
Melanie Cole (Host): Welcome to Emory Healthcare Rounds. I'm Melanie Cole. Today, you are listening to part one of our conversation on the latest advances in immunotherapy, and my guests are Dr. Bassel El-Rayes. He’s a gastrointestinal oncologist in the department of Hematology and Medical Oncology at Emory University School of Medicine and Vice Chair for Clinical Research at Winship Cancer Institute of Emory University. And Dr. Gregory Lesinski. He’s an Associate Professor in the Department of Hematology and Medical Oncology at Emory University School of Medicine and the Co-Director of Translational GI Malignancy Program at Winship Cancer Institute where his primary research interests include immunotherapeutics. Welcome to the show gentlemen. So, El-Rayes, I’d like to start with you. What is the evolution of immunotherapy and how do you see it breaking on to the cancer scene?
Dr. Bassel El-Rayes, MD (Guest): Thank you for that interesting question. For a long time, we have known that the immune therapy is a venue to treat cancer, but we have not been able to take that information from the lab into the clinic successfully. Recently, in the past few years, with the development of a new class of antibodies, called check point inhibitors, we started seeing the fruit of the work that was done for many years in the lab. We started to see drugs come into the clinic that can stimulate the immune system to fight the cancer. Of course, this is a new approach for cancer therapeutics and it appears to be a very promising approach. Since the introduction of that first class of drugs there are a number of additional classes of drugs that are now being looked at and researched in different cancers. These drugs target different aspects of the immune system, trying to stimulate the body to fight the cancer and most people in the field feel that immune therapy is the path forward for cancer therapeutics in the near future.
Melanie: And Dr. Lesinski, once of the most fascinating aspects for other physicians seems to be that immunotherapy can turn off cancer cells’ abilities to develop into tumors and how are you exploring ways to boost immune cells’ capacity to fight back. It is teaching these little soldiers as it were. Please outline for us the basic principles of cancer immunotherapy.
Dr. Gregory Lesinski, PhD, MPH (Guest): So, yeah, the basic principles of cancer immunotherapy are different than a conventional therapeutic approach for advanced malignancy in that the target of the drugs and the approaches used are really the body’s own white blood cells and immune system as opposed to interacting with the developing tumors themselves. So, this is really a paradigm shifting way to establish a living drug within the body either derived from a patient’s own immune system or even more complex cellular approaches where patient’s white blood cells are taken out of the body, educated in a certain way and put back into the body with a cancer fighting capacity in the setting of adoptive cell therapy or CAR-T cells. As Dr. El-Rayes had mentioned earlier, the immune system is activated by cancers but in many cases it is shut off, so what people are looking at including investigators at Winship Cancer Institute, are ways to overcome those shut off switches by giving drugs or in fact learning more about how cancers will paralyze the immune system through soluble factors that they may produce as well as really transformations of the way the immune system looks and functions in those patients.
So, the path forward in this whole field, is really trying to advance on this exciting data with single agent immunotherapies such as these check point inhibitor antibodies where in many patients with advanced disease, normally they would receive conventional therapy; here in many situations, they will receive these immunotherapies and have regressions of long-term metastatic disease. So, we are now looking into combination therapy approaches by combining multiple immunotherapies at the same time or with other small molecules that may target the cancer cells directly or in essence with more conventional therapies like radiotherapy or chemotherapy. All this work is ongoing, and we predict that many new exciting findings will emerge within the next few years as some of the early phase clinical trials and research completes.
Melanie: Dr. El-Rayes, as we hear about all of these different types of immunotherapy from adoptive cell transfer and even possibly vaccines, treatment vaccines; who do you envision this to be most beneficial for? Who are going to be appropriate candidates for these types of therapies?
Dr. El-Rayes: I think on the long-term hopefully it will be applied in the majority of cancers and in patients mainly who have – now it is being studied in patients who have advanced stage disease but there is interest in studying even an earlier staged disease to try and prevent cancer recurrences. So, I think this approach of using either medications to stimulate the immune system, vaccines, adoptive T-cell technologies between those different methods to stimulate the immune system will be used in treatments of the majority of cancers in the future and hopefully they will be used in early stage as well as late-stage disease.
Melanie: Dr. Lesinski, back to you. You mentioned Car-T cell therapy before and some of these types of immunotherapies can cause some side effects, some worrisome side effects. What are some of the risks and benefits that you would lay out to patients based on the fact that you are using these living – this kind of living organism to help fight their immune system?
Dr. Lesinski: Yeah, that’s a great question and a great point. Anytime you really unleash the body’s ability to react against a tissue, like a tumor that is considered self in many ways, you inherently open up the door for a variety of risks and as people have observed clinically, one of the major side effects from immune therapy are various toxicities that are autoimmune in nature and these are to be taken very seriously. Many of them can obviously be managed with steroids to quell that reaction, however, in many cases, they can in fact become quite serious.
So, these are definitely risks that need to be taken into account when a patient considers an immunotherapy type treatment approach or experimental trial, and these are also things that in the laboratory and the clinic, people are actively studying to better understand the mechanisms of those toxicities and whether the benefit is linked with appearance of them. So, just as an example, in many patients who have melanoma, skin cancer, who receive immunotherapy, they will often get a syndrome called vitiligo where the pigment is reduced in the body as a direct result of attacking melanin producing cells by the immune system. This in itself is often closely linked with efficacy of these immunotherapies, so in that essence many of these off-target effects or on target effects that are autoimmune in nature can actually be signs that the drugs are working.
So, this is a very curious area and on the flip side, there have been some recent reports I believe in the New England Journal from a Jedd Wolchok and his group at Memorial who have shown that the zealous response of the immune system against tumors such as one in maybe the bowel, metastatic melanoma when the T-cells would recognize it you can actually lead to a perforation resulting in unanticipated toxicity. So, this is a case where unlike other therapies, the side effects can result from a dramatic efficacy of treatment as well as sort of the basic autoimmune reactions that you might expect. The risks of – so that’s speaking to the risks of immunotherapy, but certainly the benefits of immune therapy are huge in that many patients again who would have progressed on multiple other treatment options can really have long durable regressions of disease and in many cases complete responses that don’t recur. A lot of this work has been seen very dramatically in lung cancer referred to as the Lazarus effect as well as in melanoma, renal cell carcinoma, and some of the colon cancers and other tumors that have micro satellite instability as a genetic marker. So, that’s sort of my understanding of the risks and benefits within the immunotherapy space and a few examples of how those might be used clinically as well as in our planning when patients are administered these agents.
Melanie: Dr. El-Rayes, Dr. Lesinski just said it might be used in planning. So, what’s going on right now as far as FDA approved treatments and he mentioned melanoma and lung cancer, we have heard of CAR-T cell for even children’s treatments of leukemia and such so where are we in FDA approval for the different types of cancer and immunotherapies?
Dr. El-Rayes: So, in the past few years, we have had a number of FDA approvals for the class of drugs called check point inhibitors. Like we said, those are antibodies that stimulate the specific type of lymphocytes to recognize the cancer. The drugs are now approved in melanoma, and lung cancer and cancers of the head and neck and then in stomach cancer, liver cancer. They are also approved recently in a special kind of colon cancer called MSI High colon cancer or otherwise known as Lynch syndrome. These are some examples of cancers that have recently – where we have recently demonstrated that check point inhibitors have clinical activity and we were able to meet bars set by the FDA to get approval for those medications. In addition, those medications are approved in some of the blood cancers like Hodgkin’s disease. Now the CAR-T cells have been approved in lymphoma and in a kind of leukemia called ALL which as you mentioned earlier affects children and then there are a number of other compounds that are getting close to being approved but not yet approved that are in late stage clinical development that target the immune system as well.
Melanie: Absolutely fascinating gentlemen. This concludes part one of our special two part series on immunotherapy. We invite you to listen to part two in order to hear the rest of this fascinating interview. Winship Cancer Institute of Emory University is an NCI comprehensive cancer center. Should you have questions or wish to discuss the care of your patients please use our referral form or call us at 888-WINSHIP, that's 888-946-7447. You're listening to Emory Healthcare Rounds. For more information on Winship Cancer Institute of Emory University, please visit www.emoryhealthcare.org/referwinship that's www.emoryhealthcare.org/referwinship . I'm Melanie Cole. Thanks so much for tuning in.